The interplay between hypothalamic neurons and microglia as they integrate stressors to regulate homeostasis is of growing interest. We asked if microglia in the embryonic hypothalamus were likewise ...stress responsive and, if so, whether their precocious activation perturbs nearby neural stem cell (NSC) programs. We performed single-cell transcriptomics to define embryonic hypothalamic microglia heterogeneity and identified four microglial subsets, including a subpopulation adjacent to NSCs that was responsive to gestational cold stress. Stress exposure elevated CCL3 and CCL4 secretion, but only in male brains, and ex vivo CCL4 treatment of hypothalamic NSCs altered proliferation and differentiation. Concomitantly, gestational stress decreased PVN oxytocin neurons only in male embryos, which was reversed by microglia depletion. Adult offspring exposed to gestational stress displayed altered social behaviors, which was likewise microglia dependent, but only in males. Collectively, immature hypothalamic microglia play an unappreciated role in translating maternal stressors to sexually dimorphic perturbation of neurodevelopmental programs.
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•Embryonic hypothalamic microglia are heterogeneous•A subpopulation of embryonic hypothalamic microglia reside adjacent to NSCs•Maternal cold stress impacts embryonic microglia signaling to nearby NSCs in males•Exposure to gestational stress leads to disrupted social behaviors in adulthood
Rosin et al. show that the embryonic hypothalamus is comprised of four unique microglial subpopulations, including one microglial cluster that responds to maternal cold stress and influence nearby NSCs in a sexually dimorphic manner, suggesting that maturing microglia play an unappreciated role in translating maternal stressors to perturbations in neurodevelopment.
Oral melphalan and dexamethasone (MDex) is a standard treatment for patients with AL amyloidosis who are not eligible for stem cell transplantation at many referral centers. However, following ...encouraging reports on the activity of bortezomib combined with alkylators and dexamethasone, these combinations are being moved to frontline therapy. We compared the outcome of 87 patients treated with bortezomib plus MDex (BMDex) with that of 87 controls treated with MDex. Patients and controls were matched for age, cardiac and renal function and free light chain burden. A higher rate of complete responses was observed with BMDex (42 vs 19%), but this did not result in a survival improvement in the overall population. However, a significant survival advantage for BMDex was observed in patients without severe (New York Heart Association class III or IV) heart failure and with N-terminal pro-natriuretic peptide type-B <8500 ng/l. Patients treated with full-dose dexamethasone had similar response rates and survival whether they received bortezomib or not. Intermediate-risk patients who are not fit enough to receive high-dose dexamethasone are likely to take the greatest advantage from the addition of bortezomib to MDex.
•Microglia play important roles in both the development and continued function of the hypothalamus throughout life.•Microglia could be key regulators of homeostasis by sensing cues external to the ...CNS and acting through the hypothalamus.•Microglial dysfunction can result in neuroendocrine diseases when proper balance is not achieved.
The hypothalamus is a crucial brain region that responds to external stressors and functions to maintain physiological homeostatic processes, such as core body temperature and energy balance. The hypothalamus regulates homeostasis by producing hormones that thereby influence the production of other hormones that then control the internal milieu of the body. Microglia are resident macrophages and phagocytic immune cells of the central nervous system (CNS), classically known for surveying the brain’s environment, responding to neural insults, and disposing of cellular debris. Recent evidence has shown that microglia are also responsive to external stressors and can influence both the development and function of the hypothalamus in a sex-dependent manner. This emerging microglia-hypothalamic interaction raises the intriguing notion that microglia might play an unappreciated role in hypothalamic control of physiological homeostasis. In this review, we briefly outline how the hypothalamus regulates physiological homeostasis and then describe how this literature overlaps with our understanding of microglia’s role in the CNS. We also outline the current literature demonstrating how microglia loss or activation affects the hypothalamus, and ultimately homeostasis. We conclude by proposing how microglia could be key regulators of homeostatic processes by sensing cues external to the CNS and transmitting them through the hypothalamus.
Both global dynamics and turbulence in magnetized weakly collisional cosmic plasmas are described by general magnetofluid equations that contain pressure anisotropies and heat fluxes that must be ...calculated from microscopic plasma kinetic theory. It is shown that even without a detailed calculation of the pressure anisotropy or the heat fluxes, one finds the macroscale dynamics to be generically unstable to microscale Alfvénically polarized fluctuations. Two instabilities that can be treated this way are considered in detail: the parallel firehose instability (including the finite Larmor radius effects that determine the growth rate and scale of the fastest growing mode) and the gyrothermal instability (GTI). The latter is a new result – it is shown that a parallel ion heat flux destabilizes Alfvénically polarized fluctuations even in the absence of the negative pressure anisotropy required for the firehose. The main physical conclusion is that both pressure anisotropies and heat fluxes associated with the macroscale dynamics trigger plasma microinstabilities and, therefore, their values will likely be set by the non-linear evolution of these instabilities. Ideas for understanding this non-linear evolution are discussed. It is argued that cosmic plasmas will generically be ‘three-scale systems’, comprising global dynamics, mesoscale turbulence and microscale plasma fluctuations. The astrophysical example of cool cores of galaxy clusters is considered quantitatively and it is noted that observations point to turbulence in clusters (velocity, magnetic and temperature fluctuations) being in a marginal state with respect to plasma microinstabilities and so it is the plasma microphysics that is likely to set the heating and conduction properties of the intracluster medium. In particular, a lower bound on the scale of temperature fluctuations implied by the GTI is derived.
Existing research on perfectionism and binge eating suggests that socially prescribed, self-oriented, and other-oriented perfectionism (Socially Prescribed Perfectionism, SPP; Self-Oriented ...Perfectionism, SOP; and Other-Oriented Perfectionism, OOP) are differentially related to binge eating. However, previous studies have largely utilized cross-sectional methodology. The present study used a 20-day daily diary methodology to examine associations between daily levels of perfectionistic dimensions and next-day binge eating behaviors with a nonclinical sample of emerging adults (N = 263). Zero-inflated negative binomial regression models indicated that daily SPP (but not SOP or OOP) predicted a greater intensity of next-day binge eating behaviors in the count portion of the model; however, daily levels of perfectionistic dimensions did not predict the presence/absence of next-day binge eating behaviors in the zero-inflated portion of the model. Additionally, analyses examining the reverse causal direction (i.e., binge eating behaviors predicting higher next-day perfectionism) failed to provide evidence that the occurrence or intensity of binge eating behaviors predicts next-day levels of SPP, SOP, or OOP. Overall, at a daily level, SPP appears to be a vulnerability factor for binge eating behaviors. It may be helpful for clinicians to target state-levels of SPP to reduce harmful binge eating behaviors.
Public Significance Statement
It has been suggested that people may be more likely to binge eat when they believe that others expect and demand perfection from them. This idea was supported by the results of this study, which showed that when a nonclinical sample of emerging adults (i.e., 18-25-year-olds) reported strongly believing that others expect and demand perfection from them (i.e., socially prescribed perfectionism), they were more likely to have more intense binge eating behaviors on days when they engaged in binge eating behaviors.
Urbanization is a process globally responsible for loss of biodiversity and for biological homogenization. Urbanization may have a direct negative impact on species behaviour and indirect effects on ...species populations through alterations of their habitats, for example patch size and habitat quality. Woodpeckers are species potentially susceptible to urbanization. These birds are mostly forest specialists and the development of urban areas in former forests may be an important factor influencing their richness and abundance, but documented examples are rare. In this study we investigated how woodpeckers responded to changes in forest habitats as a consequence of urbanization, namely size and isolation of habitat patches, and other within-patch characteristics. We selected 42 woodland patches in a gradient from a semi-natural rural landscape to the city centre of Poznań (Western Poland) in spring 2010. Both species richness and abundance of woodpeckers correlated positively to woodland patch area and negatively to increasing urbanization. Abundance of woodpeckers was also positively correlated with shrub cover and percentage of deciduous tree species. Furthermore, species richness and abundance of woodpeckers were highest at moderate values of canopy openness. Ordination analyses confirmed that urbanization level and woodland patch area were variables contributing most to species abundance in the woodpecker community. Similar results were obtained in presence-absence models for particular species. Thus, to sustain woodpecker species within cities it is important to keep woodland patches large, multi-layered and rich in deciduous tree species.
Since its inception in 2001, in utero electroporation (IUE) has been widely used by the neuroscience community. IUE is a technique developed to introduce plasmid DNA into embryonic mouse brains ...without permanently removing the embryos from the uterus. Given that IUE labels cells that line the ventricles, including radial fibers and migrating neuroblasts, this technique is an excellent tool for studying factors that govern neural cell fate determination and migration in the developing mouse brain. Whether IUE has an effect on microglia, the immune cells of the central nervous system (CNS), has yet to be investigated.
We used IUE and the pCIG2, pCIC-Ascl1, or pRFP-C-RS expression vectors to label radial glia lining the ventricles of the embryonic cortex and/or hypothalamus. Specifically, we conducted IUE at E14.5 and harvested the brains at E15.5 or E17.5. Immunohistochemistry, along with cytokine and chemokine analyses, were performed on embryonic brains with or without IUE exposure.
IUE using the pCIG2, pCIC-Ascl1, or pRFP-C-RS vectors alone altered microglia morphology, where the majority of microglia near the ventricles were amoeboid and displayed altered expression signatures, including the upregulation of Cd45 and downregulation of P2ry12. Moreover, IUE led to increases in P2ry12
cells that were Iba1
/IgG
double-positive in the brain parenchyma and resembled macrophages infiltrating the brain proper from the periphery. Furthermore, IUE resulted in a significant increase in cell death in the developing hypothalamus, with concomitant increases in cytokines and chemokines known to be released during pro-inflammatory states (IL-1β, IL-6, MIP-2, RANTES, MCP-1). Interestingly, the cortex was protected from elevated cell death following IUE, implying that microglia that reside in the hypothalamus might be particularly sensitive during embryonic development.
Our results suggest that IUE might have unintended consequences of activating microglia in the embryonic brain, which could have long-term effects, particularly within the hypothalamus.
The central tenet of European farmland ecology is that agricultural intensification during the 20th century was largely responsible for dramatic declines in species abundances. However, during this ...time, human rural settlements were also undergoing radical changes through modernization, with undocumented biodiversity impacts in this important wildlife habitat. We performed the first ever large‐scale study to disentangle the impact of these simultaneous processes on farmland bird diversity in 104 Polish villages. We show that modernized villages and their surrounding agricultural fields had 50–60% fewer birds than those in and around comparable older villages. The relative contribution of modernization versus agricultural intensification to predicted bird declines was 88% versus 12% for bird communities in villages and 56% versus 44% in surrounding croplands, with considerable variation among ecological species subgroups. These results challenge our current understanding of agricultural ecosystem ecology and how best to implement conservation measures costing billions of euros annually.
Oral lichen planus is categorized as a potentially malignant condition by the World Health Organization; however, some argue that only lichen planus with dysplasia have malignant potential. Many ...pathologists call lichen planus with dysplasia “dysplasia with lichenoid mucositis (LM)” or “LM with dysplasia.” Previous research has shown that certain high-risk patterns of loss of heterozygosity (LOH) in dysplastic lesions are associated with significantly increased cancer risk. However, LM without dysplasia lacks such molecular patterns, supporting the hypothesis that LM, by itself, is not potentially malignant and that only those with dysplasia have malignant potential. To further investigate the premalignant nature of LM with dysplasia, this study compared the rate of malignant progression of dysplasia with LM with that of dysplasia without LM. Patients from a population-based prospective cohort study with >10 y of follow-up were analyzed. Study eligibility included a histological diagnosis of a primary low-grade dysplasia with or without LM. A total of 446 lesions in 446 patients met the selection criteria; 373 (84%) were classified as dysplasia without LM, while 73 (16%) were classified as dysplasia with LM. Demographic and habit information, clinical information, and outcome (progression) were compared between the 2 groups. Forty-nine of 373 cases of dysplasia (13%) progressed compared to 8% (6/73) of dysplasia with LM. However, the difference was not statistically different (P = 0.24). The 3- and 5-y rate of progression did not differ between the groups (6.7% and 12.5% for dysplasia without LM and 2.9% and 6.6% for those with LM; P = 0.36). Progression was associated with nonsmoking, location at a high-risk site, and diagnosis of moderate dysplasia regardless of whether LM was present or not. Dysplasia with or without LM had similar cancer risk, and dysplasia should not be discounted in the presence of LM.
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